Izervay: Real-World Data Shows IOP Increase, AMD Conversion Risk

New data published in the Journal of VitreoRetinal Diseases offer a real-world look at the safety profile of avacincaptad pegol, marketed as Izervay, for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). While the medication has demonstrated efficacy in slowing the progression of GA in clinical trials, this retrospective analysis provides valuable insight into potential adverse events observed in a broader patient population.

Intravitreal Injections and Potential Complications

Izervay is administered via intravitreal injection, a procedure where medication is directly injected into the vitreous humor of the eye. As with any injection, there are inherent risks. The study, conducted by researchers at Retina Group of Washington, analyzed data from 461 eyes of 335 patients treated between August 3, 2023, and October 10, 2024. Patients received an average of 3.33 injections over an average follow-up period of 120 days, with injections occurring at roughly 52-day intervals.

The researchers identified an acute increase in intraocular pressure (IOP) in 3% of eyes immediately following injection. In some cases, this resulted in no light perception, requiring intervention. Three eyes underwent anterior chamber paracentesis, a procedure to lower IOP, while vision recovered in other eyes without this intervention. This finding underscores the importance of careful monitoring of IOP following each injection.

Conversion to Wet AMD: A Potential Concern

Perhaps the most notable finding of the study was the observed rate of conversion from dry AMD to wet AMD. Eight eyes (2.03%) progressed to wet AMD during the follow-up period. These eyes had received an average of two injections prior to conversion, with a maximum of three. Based on this data, the researchers calculated an annualized wet AMD conversion rate of 6.17%.

This conversion rate is a critical consideration. Wet AMD is a more aggressive form of the disease that typically requires ongoing treatment with anti-VEGF injections to prevent vision loss. The potential for Izervay to, in some cases, trigger the development of wet AMD raises questions about patient selection and the long-term risk-benefit profile of the medication.

Other Adverse Events and Long-Term Safety

In addition to IOP increases and conversion to wet AMD, one eye experienced vitreous hemorrhage. Importantly, the study found no cases of endophthalmitis (a severe intraocular infection), intraocular inflammation, or nonarteritic anterior ischemic optic neuropathy. These are all potentially serious complications associated with intravitreal injections, and their absence in this study is reassuring.

The authors emphasize that the long-term safety profile of avacincaptad pegol remains unknown. Additional research with larger sample sizes and extended follow-up durations is needed to fully understand the medication’s potential risks and benefits.

Contextualizing the Findings

As noted in a perspective piece accompanying the study, authored by Caitlyn Williams, OD, MPH, FAAO, of the Birmingham VA Medical Center and the University of Alabama at Birmingham School of Optometry, this real-world data is valuable but should be interpreted with caution. The retrospective design and lack of a control group limit the ability to definitively attribute observed events to the medication itself. For example, the 6.17% annualized wet AMD conversion rate cannot be directly compared to the natural conversion rate in a similar patient population without a control group.

Dr. Williams also points out that the study does not assess the efficacy of Izervay in slowing the progression of GA. It is difficult to weigh the potential risks against the potential benefits. A complete assessment requires data on both safety and efficacy.

Implications for Clinical Practice

The findings of this study provide clinicians with valuable information as they consider incorporating complement inhibitor therapies, like Izervay, into their clinical practice. The data highlight the importance of careful patient selection, thorough pre- and post-injection monitoring, and a clear understanding of the potential risks and benefits. While Izervay offers a promising new treatment option for GA, it is not without potential adverse effects. Ongoing research and careful clinical judgment will be essential to optimize patient outcomes.

The researchers conclude that this study “may be helpful to clinicians as they decide how to incorporate complement inhibitor therapies in their clinical practice,” but reiterate the need for further investigation to fully elucidate the medication’s long-term safety profile.